Cholesterol: Synthesis, Metabolism, Regulation

It causes shortening of the carbon chain from 30 to 27 carbons, removal of the two methyl groups at carbon 4, migration of the double bond from carbon 8 to carbon 5, and reduction of the double bond between carbon 24 and carbon 25.
~ Synthesis requires enzymes in both the cytosol and the membrane of the smooth endoplasmic reticulum (ER).

~ The pathway is responsive to changes in cholesterol concentration, and regulatory mechanisms exist to balance
the rate of cholesterol synthesis within the body against the rate of
cholesterol excretion.



► Inhibition of cholesterol biosynthesis is a signal for cell proliferation.

Cholesterol biosynthesis from lanosterol

A third molecule of acetyl CoA is added, producing HMG CoA, a six-carbon compound.
Synthesis of Mevalonate
~ The next step, the reduction of HMG CoA to mevalonate, is catalyzed by HMG CoA reductase.
~ It is the rate-limiting and key regulated step in cholesterol synthesis.

While cholesterol synthesis is mostly associated with eukaryotes, ..

In addition, we determined serum concentrations of lanosterol, a precursor of cholesterol and a possible indicator of cholesterol biosynthetic activity.

► Mutated p53 forms activate cholesterol biosynthesis genes expression.

Steroidal Triterpenes of Cholesterol Synthesis - MDPI

Cholesterol is an important biochemical, medical, and commercial molecule. In the pathway for cholesterol biosynthesis, biochemistry textbooks discuss the synthesis of lanosterol from acetate in detail. However, the conversion of lanosterol to cholesterol is most often simply indicated as a multistep process, without elaboration. A pathway for the conversion of lanosterol to cholesterol, based on recent results from the primary research literature, is presented in this paper. Each reaction is discussed, the pathway is discussed within the context of general biochemical transformations, a summary of cholesterol homeostasis is presented, and enzyme deficiencies that give rise to diseases are given.

► Mutated p53 forms activate cholesterol biosynthesis genes expression."


Synthesis of cholesterol
- Cholesterol is synthesized by virtually all tissues in humans, although liver, intestine, adrenal cortex, and reproductive tissues, including
ovaries, testes, and placenta, make the largest contributions to the body’s cholesterol pool.

- The pathway is endergonic, being driven by hydrolysis of the high-energy thioester bond of acetyl coenzyme A (CoA) and the terminal
phosphate bond of adenosine triphosphate (ATP).
Synthesis of 3-hydroxy-3-methylglutaryl (HMG) CoA
- The first two reactions in the cholesterol synthetic pathway are similar to those in the pathway that produces ketone bodies .
- They result in the production of HMG CoA .

There was no association between the individual change in serum cholesterol and the change in cholesterol synthesis.

Progesterone Inhibits Cholesterol Biosynthesis in …

The effects of oxygenated lanosterol derivatives (1-14) on cholesterol biosynthesis from [24-3H]-lanosterol were tested in 10000×g supernatant (S10) fraction of rat liver homogenate (RLH). Among the derivatives studied, 7-oxo-24, 25-dihydrolanosterol (11) was most active in depressing cholesterol biosynthesis from lanosterol. The inhibitory activities of these derivatives on cholesterol synthesis are discussed in relation to the position and stereochemistry of the oxygen group on the side chain and the sterol nucleus.

The decrease in cholesterol intake caused an increase in cholesterol synthesis in five out of the six subjects.

Effects of Steroid Hormones on Synthesis of Cholesterol …

Synthesis of Cholesterol
~ Cholesterol is a very hydrophobic compound.
~ It consists of four fused hydrocarbon rings (A-D) called the “steroid nucleus”)
~ It has an eight-carbon, branched hydrocarbon chain attached to carbon 17 of the D ring.